1Department of Neurology and Stroke Center, Firoozgar General Hospital, Iran University of Medical Sciences,Tehran 1449614535, Iran2Iran University of Medical Sciences, Tehran 1449614535, Iran3Students’ Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran 1417755331, Iran
Correspondence should be addressed to Shooka Esmaeeli; [email protected]
Received 28 September 2014; Revised 21 December 2014; Accepted 9 January 2015
Introduction. Differentiating pseudopapilledema from papilledema which is optic disk edema and a result of increased ICP(intracranial pressure) is important and can be done with noninvasive methods like orbital ultrasound examination.Method. Thiswas a cross-sectional study in which patients with optic nerve head swelling were referred for LP exam after optic nerve headswelling diagnosis confirmation and having normal brain imaging (CT scan). Before LP (lumbar puncture) exam the patients werereferred for optic nerve ultrasound test of both eyes. Results. Considering 5.7mm as the upper limit for normal ONSD (optic nervesheath diameter), sensitivity and negative predictive value of optic sonography in diagnosis of pseudopapilledema are 100% for botheyes. Calculated accuracy validity of ONSDmeasurement in detecting pseudopapilledema is 90% for the right eye and 87% for theleft eye. Conclusion. Our study demonstrated a close correlation between optic nerve sheath dilation on ocular ultrasound andevidence of elevated ICP with optic disk swelling. With the aid of noninvasive diagnostic tests we can avoid unnecessary concernsalong with expensive and invasive neurological investigations while targeting the correct diagnosis in bilateral optic disk swelling.Our study showed optic nerve sonography as a reliable diagnostic method for further usage.
1. Introduction
While papill edema is Optic Nerve Head (ONH) edema sec-ondary to increased intracranial pressure (ICP), pseudopa-pilledema is apparent ONH swelling that stimulates somefeatures of papill edema but is secondary to an underlying,usually benign, process which can be congenital anomaliesassociated with the disk elevation, hyperopic disk, or ONHdrusen.
Acquired disk edema includes papilledema as well asother causes of optic disk edema such as optic neuritis,anterior ischemic optic neuropathy, malignant hypertension,
infiltrative optic neuropathies, and compressive optic neu-ropathy [1].
ONH drusen accounts for 75% of clinical cases of pseu-dopapilledema, occurs in up to 2% of general population, andis congenitally inherited; it has the same prevalence betweenmen and women and is usually bilateral. Patients with ONHdrusen are usually asymptomatic but visual field defects canbe present.
Diagnosis is most reliably made by orbital ultrasoundexamination [1].
Clinical features in pseudopapilledema differ from papill-edema; pseudopapilledema patients usually have no visual
Hindawi Publishing CorporationNeurology Research InternationalVolume 2015, Article ID 146059, 4 pageshttp://dx.doi.org/10.1155/2015/146059
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symptoms while papilledema patients can have the follow-ing symptoms: transient visual obscurations, blurring ofvision, diplopia, decreased color perception, and so forth.Also papilledema is almost always bilateral while pseudopa-pilledema can be either bilateral or unilateral. Furthermorethere are some funduscopic assessment features seen in truepapilledema which can help to distinguish it from pseudopa-pilledema, such as hyperemia of the optic disk with surfacetelangiectatic vessels, congested vasculature, and associatedflame hemorrhages, optic disk elevation, and blurring of thedisk margin associated with obscuration of the retinal vesselsthat traverse it. Lack of spontaneous venous pulsations at diskmargin suggests true papilledema, but it is not diagnostic [1].
ONH elevation tends to be the most intimidating ocularfinding especially when it presents bilaterally. The fore-most clinical aim is to differentiate pseudopapilledema fromacquired disk edema. Papilledema is ONH edema as a resultof increased ICP, which bears specific etiologic implications.The most important entity to consider in cases of increasedICP is a space occupying lesion of the brain. A throughhistory and a dilated fundus examination with use of currentdiagnostic technologies can facilitate the diagnosis. Orbitalultrasound examination is reported to be a useful noninvasiveway which increase our ability to diagnose and manage thesechallenging case scenarios [2–5].
The purpose of this paper is to provide clinical strategiesthat will enhance clinicians’ assessment of bilateral diskelevations. In addition, this topic is important to reviewbecause effective management will reduce over referrals forneurological evaluations, thus decreasing health care costswhile avoiding LP, which is the gold standard test for ICPmeasuring, and other expensive imaging technologies.
2. Method
This was a cross-sectional study in 2013-2014, in which 32(64 eyes) patients with bilateral ONH swelling whom hadvisited the ophthalmology or neurology clinic of FiroozgarHospital, located in Tehran, Iran, were included.We excludedpatients who had contraindication for LP such as increasedintracranial pressure due to brain mass, bleeding diathesissuch as coagulopathy and thrombocytopenia, skin infectionat puncture site, sepsis, abnormal respiratory pattern, focalneurologic deficit, and loss of consciousness. Ophthalmicevaluation was done by expert ophthalmologist to rule outother causes. Also computerized tomography (CT) scan wasdone for all of the patients; if it did show any mass orabnormality which could be the reason for optic disk edema,the patient must be excluded.
We explained the process of our research for all includedpatients before starting data gathering. We asked them tosign written testimonials if they accept being included; alsothey had the choice to stop cooperating with our projectwhenever they want. Furthermore we have to point thatour study was noninvasive and did not harm any body andwe respected Helsinki declaration all along our project. Weobtained ethical approval and it was not a part of routine care.
Table 1: Results (RT = right, LT = left, OND = optic nerve diameter,and ONSD = optic nerve sheath diameter).
The patients were referred for LP exam after ONHswelling diagnosis confirmation and normal brain imaging.Before LP exam we had measured the vertical and horizontaldiameters of the optic nerves of both eyes by ultrasonography(US) in supine position.The probewas placed on the superiorand lateral aspect of the orbit against the upper eyelid withthe eye closed and angled slightly caudally and mediallyuntil the optic nerve was visualized as a linear hypoechoicstructure with clearly defined margins posterior to the globe.The probe was always placed gently on the closed eyelidwithout any contact with the cornea or sclera. Contact withthe eye was gentle and pressure never directly applied on theglobewith the probe, as this can theoretically result in nausea,vomiting, and a vagal response. The ONSD was measured3mm behind the retina; the measurements were done bywetting the closed eyelids and using a 7.5MHz linear probe.All of the measurement in optic sonography was done byexpert and particular person. We compare the ultrasoundresults with the LP results as the gold standard of measuringICP for each patient.
Statistical Analysis. All analysis and comparisons were donewith SPSS version 16. The mean of right and left eyes ONSD(optic nerve sheath diameter), OND (optic nerve diameter),and CSF pressure were calculated. A receiver operatingcharacteristic (ROC) curve was constructed to determine theoptimal ONSD and OND cut-off to detect ICP > 20mmHg.We calculated the sensitivity and specificity of this cut-offwith 95% confidence intervals for the detection of ICP >20mmHg. Also the sensitivity, specificity, positive predictivevalue, negative predictive value, and accuracy validity ofoptic sonography were calculated for detecting of pseudopa-pilledema. At last we calculate the diagnostic accuracy whichis in fact a criterion that considers sensitivity and specificitytogether for determination of optic sonography value indiagnosis of pseudopapilledema.
3. Results
We performed ocular sonography on 29 female and 3 malepatients with swelled optic disk.Themean age of patients was35.44 ± 13 (19–75 years old). 19 patients were below 35 yearsold and 13 were older than 35 (Table 1).
According to the literatures we set 5.7mm and 20mmHgas the cut-off values forONSD andCSF pressure, respectively.We measured CSF pressure, RT.ONSD, and LT.ONSD inpatients. Results show that 68.8% (22 patients) of the patientshad CSF pressure more than 20mmHg, and for 81.4% (26
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Table 2: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy validity of optic sonography in diagnosis ofPPE.
Sensitivity Specificity Positive predictive value Negative predictive value Accuracy validityRT.ONSD 100 84 60 100 90LT.ONSD 100 88 70 100 87Both eyes together 100 83 55 100 86
patients) and (25 patients) 78% of patients RT.ONSD andLT.ONSD were more than the chosen threshold, respectively.
Due to our measurements, patients with high ICP hadsignificantly larger ONSD comparing to the patients withnormal ICP (right ONSD, OR: 5.2mm, 𝑃 = 0.001, Kappa:0.67 and for left ONSD OR: 4.1mm, 𝑃 = 0.002, Kappa: 0.76).Additionally comparing OND of patients with high ICP withones with normal ICP demonstrates the significantly higherOND in patients with high ICP (RTOND,OR: 1.15,𝑃 = 0.000and for LT OND OR: 1.20, 𝑃 = 0.000).
Considering 5.7mm as the upper limit for normal ONSD,sensitivity, specificity, positive predictive value, negative pre-dictive value, and accuracy validity of optic sonography indiagnosis of PPE are shown in Table 2.
Due to the lack of enough male subjects we couldnot assess the accuracy validity of ONSD measurement indetecting pseudopapilledema based on gender. Based on themeasurements age did not affect accuracy validity of opticsonography for detecting pseudopapilledema (RT.ONSD sig:0.497 and LT.ONSD sig: 0.21).
The area under the curve (AUC) for RT.ONSD andLT.ONSD is 0.8 and 0.91 (𝑃 < 0.01 for AUC = 0.5),respectively. The best RT.ONSD cut-off value for detection ofinvasive ICP > 20mmHg is 5.95mmwith 86% sensitivity and70% specificity.The best LT.ONSD cut-off value for detectionof invasive ICP > 20mmHg is 5.86mm. The sensitivity ofthis cut-off is 90% and the specificity is 80%.The best ONSDcut-off for both eyes together is 5.91mm (sensitivity 86%,specificity 75%, AUC 0.85, 𝑃 < 0.000) (Figure 1).
The best RT.OND cut-off for the detection of invasive ICP> 20mmHg is 3.15mm (sensitivity 78%, specificity 66%, AUC0.8, 𝑃 < 0.01). The best LT.OND cut-off for the detection ofinvasive ICP > 20mmHg is 3.19mm (sensitivity 85%, speci-ficity 63%, AUC 0.74,𝑃 < 0.04).We also calculatedOND cut-off for both eyes together that was 3.19mm (sensitivity 82%,specificity 59%, AUC 0.77, 𝑃 < 0.001).
4. Discussion
Our study demonstrates that optic nerve ultrasound withmeasurement of ONSD (optic nerve sheath diameter) isa highly accurate noninvasive technique for detection ofintracranial hypertension. The literature, supporting ourdata, has reports of correlation between ONSD and intracra-nial hypertension among intracranial hemorrhagic patients[2] and based on considering 7.3mm as the upper limit ofnormal ONSD [3]. Correspondingly some reports show thatoptic nerve ultrasound can be delightfully helping for ICPraising diagnosis when other imaging methods or invasiveneurological testing is contraindicated in patients [4, 5].
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Figure 1: Roc diagram showing correlation of total ONSD and theCSF pressure.
Also in our research based on considering 5.7mm asthe upper limit of normal ONSD for detecting ICP morethan 20 cmHg, the sensitivity and negative predictive valueof optic nerve ultrasound in diagnosis of pseudopapilledemafor the right and left eyes were 100%. There are differentreports for sensitivity and negative predictive values amongliteratures; Rajajee et al., by assessing ONSD in 56 patientswith head trauma, intracranial hemorrhage, ischemic stroke,and cranial tumor, found that ICP raising correlates withONSD in optic nerve ultrasound. With ROC curve andanalysis they demonstrated that the optimal cut-off for ICP >20 cmHg is 4.8 cm for both eyes with 96% sensitivity and94% specificity [6]. Moreover, Major et al. assessed ONSDin 26 patients. They showed that the optimal ONSD cut-offfor increased ICP is 5mm with 86% sensitivity and 100%specificity [7]. There are different sensitivity and specificityvalues for different cut-off chosen for ONSD demonstratingincreased ICP among literatures [8, 9].These different reportscould be as a matter of fact that each research has differentpopulation with different epidemiologic features and alsodifferent number of subjects; furthermore choosing lowermeasures for ONSD cut-off in optic nerve ultrasound canaffect the statistical values in this regard. To the authors’knowledge, there are not many reports for assessing a reliableONSD cut-off among Iranian population [10]; also there arenot many reports for assessing correlation betweenOND andICP raising among literature which make our research novel.
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There are some reports among literature which chose theircut-off 5.7mm in the same way as we did [11, 12]. On theother hand, there are many of reports that chose a lower cut-off which has a wide threshold among different researchesfrom 4mm tomore than 5mm [8, 9]. Besides we found somedifferent data for ONSD and OND in detecting of raisedICP in comparison of left and right eye together that wasnot considered in other researches. All these different reportscontribute to one similar conclusion; optic nerve ultrasoundis a reliable diagnostic test for detecting raised ICP.
One limitation of our study was our sample size; therewould be lower measure for our ONSD cut-off if we chose alarger sample size. Another limitationwas that only suspectedpseudotumor cerebri patients were included with normalneuroimaging and hencemore female patients were included.We could not find any relationship between gender andONSD because about 90% of our subjects were female. Thisissue could be considered for further researches that female’sand male’s ONSD cut-off could be different or not.
5. Conclusion
Our study demonstrated a close correlation between opticnerve sheath dilation on ocular ultrasound and evidence ofelevated ICP with optic disk swelling. As mentioned beforeONH swelling hasmany differential diagnoses but the criticalone is true papilledema which could be a sign of raised ICPand a serious brain problem which need urgent intervention.Hence, clinicians must rule out pathological presentationsthat can be misinterpreted as swollen anomalous nerveswhich are called pseudopapilledema. Our study showed opticnerve sonography as a reliable diagnostic method in thisregard for further usage.
Conflict of Interests
The authors declare that there is no conflict of interestsregarding the publication of this paper.
Authors’ Contribution
Masoud Mehrpour carried out the overall studies and par-ticipated in the design of the study and had active role inacquisition of data. Fatemeh Oliaee Torshizi participated inthe design of the study, performed the statistical analysis andparticipated in data gathering, and had given final approvalof the version to be published. Shooka Esmaeeli draftedthe paper, participated in the data gathering and helpedin performing the statistical analysis. Salameh Taghipourparticipated in the design of the study and coordination andhelped to draft the paper and, she also participated in thesequence alignments. Sahar Abdollahi helped to draft thepaper, participated in performing the statistical analysis, andhelped in data gathering. All authors read and approved thefinal paper.
Acknowledgment
The authors thank the Firoozgar Hospital OphthalmologyDepartment who refer the patients with whit optic diskedema to our department.
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